The overall objectives of the proposed research are: (1) prediction of safe occupational exposure to noxious gases with respect to exposure duration, concentration variation, physiological conditions of exposed subjects, and exposure to other xenobiotics, and (2) design of effective system for monitoring biological samples for evaluation of exposure. This is to be done by further refining an already-developed compartmentalized mathematical model, which is described by a set of differential equations using predictible constants, and by developing a mathematical formulation of the effects of the factors modifying overall metabolism of inhaled substances (exposure concentration, exposure to mixtures of vapors, interaction with commonly used drugs, age, pregnancy) by means of information derived from animal models. The refined mathematical model will be used to predict and quantitate the effect of each factor on uptake, distribution, cumulation, and clearance of inhaled vapors and gases. The information needed for mathematical formulation of the effect of studied factor will be obtained in experiments in two animal species models: rhesus monkey will be used for studies of enzymatic kinetics in vivo. Rats will be used for determination of tissue-air concentration gradients of vapros at steady state, and for determination of metabolites bound to cellular constituents. In order to improve exposure evaluation through monitoring of biological data (vapor concentrations in exhaled air or in blood), we will search for a simple and accurate formula to relate monitored data to sampling time and eventually to relate monitored data to environmental and physiological factors.